Using a model of profound cardiac failure (zero ejection fraction), based on producing extensive subendocardial infarction in standing, unanesthetized sheep by inducing ventricular fibrillation while maintaining the circulation with total biventricular bypass, the dynamics of the process of myocardial recovery of pumping ability (pressure-dimension analysis) and use of the biventricular bypass system to alter ventricular volume-pressure loading) will be studied in regard to both: 1) the metabolic response of the myocardium to the ischemic-hypoxic insult from biochemical analyses of snap-frozen, transmural myocardial biopsies and study of mitochondrial function; and (2) the structural response of the myocardium, reflecting both irreversible and reversible damage using a combination of gross and microscopic histochemical techniques and ultrastructural examination. These studies will be correlated with assessments of regional myocardial blood flow distribution throughout the recovery period using the radioactive microsphere technique. This model is unique in providing a stable hemodynamic environment for the heart in what would otherwise be the circumstance of fatal cardiogenic shock and has specific functional endpoints during recovery consisting of return of LV ejection in 11/2 days, return of LV function in 3 days, and unsupported myocardial recovery in 5 days. This model will allow us to test our major working hypotheses: (1) that a large zone of reversibly injured myocardium exists following global ischemic injury, which can be characterized biochemically and ultrastructurally, and evolves to full functional recovery over a 3 to 7 day period; (2) that increasing degrees of "resting" the myocardium (mechanical plus pharmocological preservation) promote more rapid recovery of pumping function; and (3) prolonged, mechanical support of the ischemically damaged myocardium provides no further advantage in providing improved recovery of pumping function and/or resersal of biochemical-ultrastructural abnormalities.